Publications by authors named "Sierra A Walker"

8 Publications

  • Page 1 of 1

Extracellular vesicle glucose transporter-1 and glycan features in monocyte-endothelial inflammatory interactions.

Nanomedicine 2022 06 22;42:102515. Epub 2022 Jan 22.

Department of Biochemistry and Molecular Biology, Department of Physiology and Biomedical Engineering, Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA; Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD, Australia (present affiliation); School of Chemical Engineering, University of Queensland, Brisbane, QLD, Australia (present affiliation). Electronic address:

Monocyte-induced endothelial cell inflammation is associated with multiple pathological conditions, and extracellular vesicles (EVs) are essential nanosized components of intercellular communication. EVs derived from endotoxin-stimulated monocytes were previously shown to carry pro-inflammatory proteins and RNAs. The role of glucose transporter-1 (GLUT-1) and glycan features in monocyte-derived EV-induced endothelial cell inflammation remains largely unexplored. This study demonstrates that EVs derived from endotoxin-stimulated monocytes activate inflammatory pathways in endothelial cells, which are partially attributed to GLUT-1. Alterations in glycan features and increased levels of GLUT-1 were observed in EVs derived from endotoxin-stimulated monocytes. Notably, inhibition of EV-associated GLUT-1, through the use of fasentin, suppressed EV-induced inflammatory cytokines in recipient endothelial cells.
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http://dx.doi.org/10.1016/j.nano.2022.102515DOI Listing
June 2022

Effects of Adipose-Derived Biogenic Nanoparticle-Associated microRNA-451a on Toll-like Receptor 4-Induced Cytokines.

Pharmaceutics 2021 Dec 22;14(1). Epub 2021 Dec 22.

Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL 32224, USA.

Extracellular vesicles (EVs) are cell-released nanoparticles that transfer biomolecular content between cells. Among EV-associated biomolecules, microRNAs (miRNAs/miRs) represent one of the most important modulators of signaling pathways in recipient cells. Previous studies have shown that EVs from adipose-derived mesenchymal stromal cells (MSCs) and adipose tissue modulate inflammatory pathways in macrophages. In this study, the effects of miRNAs that are abundant in adipose tissue EVs and other biogenic nanoparticles (BiNPs) were assessed in terms of altering Toll-like receptor 4 (TLR4)-induced cytokines. TLR-4 signaling in macrophages is often triggered by pathogen or damage-induced inflammation and is associated with several diseases. This study demonstrates that miR-451a, which is abundant in adipose tissue BiNPs, suppresses pro-inflammatory cytokines and increases anti-inflammatory cytokines associated with the TLR4 pathway. Therefore, miR-451a may be partially responsible for immunomodulatory effects of adipose tissue-derived BiNPs.
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http://dx.doi.org/10.3390/pharmaceutics14010016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780819PMC
December 2021

A Simple and Quick Method for Loading Proteins in Extracellular Vesicles.

Pharmaceuticals (Basel) 2021 Apr 13;14(4). Epub 2021 Apr 13.

Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL 32224, USA.

Extracellular vesicles (EVs) mediate intercellular transport of biomolecular cargo in the body, making them promising delivery vehicles for bioactive compounds. Genetic engineering of producer cells has enabled encapsulation of therapeutic proteins in EVs. However, genetic engineering approaches can be expensive, time-consuming, and incompatible with certain EV sources, such as human plasma and bovine milk. The goal of this study was to develop a quick, versatile, and simple method for loading proteins in EVs post-isolation. Proteins, including CRISPR associated protein 9 (Cas9), were bound to cationic lipids that were further complexed with MDA-MB-231 cell-derived EVs through passive incubation. Size-exclusion chromatography was used to remove components that were not complexed with EVs. The ability of EVs to mediate intracellular delivery of proteins was compared to conventional methods, such as electroporation and commercial protein transfection reagents. The results indicate that EVs retain native features following protein-loading and obtain similar levels of intracellular protein delivery as conventional methods, but display less toxicity. This method opens up opportunities for rapid exploration of EVs for protein delivery.
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http://dx.doi.org/10.3390/ph14040356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069621PMC
April 2021

Education and Outreach in Physical Sciences in Oncology.

Trends Cancer 2021 01 7;7(1):3-9. Epub 2020 Nov 7.

Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, USA; Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA; Center for Immunotherapeutic Transport Oncophysics, Houston Methodist Research Institute, Houston, TX, USA. Electronic address:

Physical sciences are often overlooked in the field of cancer research. The Physical Sciences in Oncology Initiative was launched to integrate physics, mathematics, chemistry, and engineering with cancer research and clinical oncology through education, outreach, and collaboration. Here, we provide a framework for education and outreach in emerging transdisciplinary fields.
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http://dx.doi.org/10.1016/j.trecan.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895467PMC
January 2021

Brain metastases-derived extracellular vesicles induce binding and aggregation of low-density lipoprotein.

J Nanobiotechnology 2020 Nov 7;18(1):162. Epub 2020 Nov 7.

Department of Biochemistry and Molecular Biology, Department of Physiology and Biomedical Engineering, Department of Transplantation, Mayo Clinic, Jacksonville, FL, 32224, USA.

Background: Cancer cell-derived extracellular vesicles (EVs) have previously been shown to contribute to pre-metastatic niche formation. Specifically, aggressive tumors secrete pro-metastatic EVs that travel in the circulation to distant organs to modulate the microenvironment for future metastatic spread. Previous studies have focused on the interface between pro-metastatic EVs and epithelial/endothelial cells in the pre-metastatic niche. However, EV interactions with circulating components such as low-density lipoprotein (LDL) have been overlooked.

Results: This study demonstrates that EVs derived from brain metastases cells (Br-EVs) and corresponding regular cancer cells (Reg-EVs) display different interactions with LDL. Specifically, Br-EVs trigger LDL aggregation, and the presence of LDL accelerates Br-EV uptake by monocytes, which are key components in the brain metastatic niche.

Conclusions: Collectively, these data are the first to demonstrate that pro-metastatic EVs display distinct interactions with LDL, which impacts monocyte internalization of EVs.
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http://dx.doi.org/10.1186/s12951-020-00722-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648399PMC
November 2020

Glycan Node Analysis of Plasma-Derived Extracellular Vesicles.

Cells 2020 08 22;9(9). Epub 2020 Aug 22.

Department of Biochemistry and Molecular Biology, Department of Physiology and Biomedical Engineering, Department of Transplantation, Mayo Clinic, Jacksonville, FL 32224, USA.

Blood plasma is a readily accessible source of extracellular vesicles (EVs), i.e., cell-secreted nanosized carriers that contain various biomolecules, including glycans. Previous studies have demonstrated that glycans play a major role in physiological and pathological processes, and certain plasma glycans have been associated with disease conditions. However, glycome studies have been limited by a lack of analytical techniques with the throughput capacity necessary to study hundreds of clinical samples. This study is the first to characterize the EV plasma glycome based on all major glycan classes. The results based on glycan node analysis revealed, as expected, that plasma-derived EVs have distinct glycan features from donor-matched whole plasma. Specifically, glycan nodes corresponding to those observed in chondroitin sulfate, dermatan sulfate, type I keratan sulfate, and type II keratan sulfate were enriched on EVs. The identification of specific differences in glycan features in plasma vs. plasma-derived EVs is relevant for understanding the physiological role of EVs and as a reference for future diagnostic studies. Additionally, the results indicate that EV glycan nodes do not substantially differ among a small set of healthy donors. These results lay the framework for the further evaluation of all EV glycan classes as diagnostic markers, therapeutic targets, and biologically active components in health and disease.
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http://dx.doi.org/10.3390/cells9091946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563425PMC
August 2020

Lipoprotein-based drug delivery.

Adv Drug Deliv Rev 2020 11;159:377-390. Epub 2020 Aug 11.

Department of Biochemistry and Molecular Biology, Department of Physiology and Biomedical Engineering, Department of Transplantation, Mayo Clinic, Jacksonville, FL 32224, USA; Department of Biology, University of North Florida, Jacksonville, FL 32224, USA; Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address:

Lipoproteins (LPs) are circulating heterogeneous nanoparticles produced by the liver and intestines. LPs play a major role in the transport of dietary and endogenous lipids to target cells through cell membrane receptors or cell surface-bound lipoprotein lipase. The stability, biocompatibility, and selective transport of LPs make them promising delivery vehicles for various therapeutic and imaging agents. This review discusses isolation, manufacturing, and drug loading techniques used for LP-based drug delivery, as well as recent applications for diagnosis and treatment of cancer, atherosclerosis, and other life-threatening diseases.
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http://dx.doi.org/10.1016/j.addr.2020.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747060PMC
August 2021

AIF promotes a JNK1-mediated cadherin switch independently of respiratory chain stabilization.

J Biol Chem 2018 09 9;293(38):14707-14722. Epub 2018 Aug 9.

From the Department of Chemistry and Biochemistry, North Dakota State University, Fargo, North Dakota 58108 and

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein occasionally involved in cell death that primarily regulates mitochondrial energy metabolism under normal cellular conditions. AIF catalyzes the oxidation of NADH , yet the significance of this redox activity in cells remains unclear. Here, we show that through its enzymatic activity AIF is a critical factor for oxidative stress-induced activation of the mitogen-activated protein kinases JNK1 (c-Jun N-terminal kinase), p38, and ERK (extracellular signal-regulated kinase). AIF-dependent JNK1 signaling culminates in the cadherin switch, and genetic reversal of this switch leads to apoptosis when AIF is suppressed. Notably, this widespread ability of AIF to promote JNK signaling can be uncoupled from its more limited role in respiratory chain stabilization. Thus, AIF is a transmitter of extra-mitochondrial signaling cues with important implications for human development and disease.
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http://dx.doi.org/10.1074/jbc.RA118.004022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153284PMC
September 2018
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